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Aim: To compare the Croatian and European population in terms of allele frequencies of clinically relevant polymorphisms in drug absorption, distribution, metabolism, and excretion (ADME) genes. Methods: In 429 Croatian participants, we genotyped 27 loci in 20 ADME genes. The obtained frequencies were merged with the published frequencies for the Croatian population by sample size weighting. The study sample obtained in this way was compared with the average data for the European population from the gnomAD database. Results: Variant allele frequencies in the Croatian population were higher in three and lower in two polymorphisms (Benjamini-Hochberg-corrected P values: 0.0027 for CYP2B6*4 rs2279343, CYP2C9*2 rs1799853, and VKORC1 rs9923231 ; 0.0297 for GSTP1 rs1695 ; 0.0455 for CYP2A6 rs1801272) compared with the European population. The most marked difference was observed for CYP2B6*4 (9.3% in Europe vs 24.3% in Croatia). The most clinically relevant findings were higher variant allele frequencies in two polymorphisms related to lower warfarin requirements: VKORC1*2 (34.9% in Europe vs 40.1% in Croatia) and CYP2C9*2 (12.3% in Europe vs 14.7% in Croatia). This indicates that three- quarters of Croatian people have at least one variant allele at these loci. Variants in genes GSTP1 and CYP2A6 were significantly less frequently observed in Croatia. Conclusions: Croatian population has a higher bleeding and over-anticoagulation risk, which is why we recommend the prescription of lower doses of anticoagulation drugs such as warfarin and acenocoumarol. Lower phenytoin, and higher bupropion and efavirenz doses are also recommended in the Croatian population.

When overexpressed, a large transmembrane P-glycoprotein, the product of the ABCB1 gene, is a notable impediment to brain-targeted therapies (like antiepileptics) and chemotherapies. Some of the genetic biomarkers with evidence of multi-drug resistance in ABCB1 ― rs1045642, rs1128503, and rs3213619 ― were analyzed in 440 subjects, members of three socio-culturally different Roma (Gypsy) groups of Croatia. Minor allele frequencies (MAFs) of rs1045642 and rs1128503 were the highest in the Balkan Roma (63.6% and 69.4%, respectively) when compared to the Baranja (52.3% and 62.5%) and the Međimurje Roma (48.8% and 54.5%) (p=0.0005 and p=0.0011, respectively). rs3213619 was monomorphic in the Međimurje group, while its MAFs in other two Roma groups were very low (

Aim: To determine variation of CYP2B6 gene within the genetically specific Croatian Roma (Gypsy) population originating from India and to examine it in the worldwide perspective. Materials & methods: Seven SNP loci (rs12721655, rs2279343, rs28399499, rs34097093, rs3745274, rs7260329 and rs8192709) were genotyped in 439 subjects using Kompetitive Allele Specific PCR (KASP) method. Results: The Croatian Roma took an outlying position in CYP2B6 variation from the worldwide perspective mainly due to their exceptionally high minor allele frequency (MAF) for rs8192709 (12.8%), and lower for rs2279343 (21.1%) compared with south Asian populations. Conclusion: This study provides the first data of several CYP2B6 polymorphisms in Roma population and indicates the need for systematic investigation of the most important pharmacogenes’ variants in this large, transnationally isolated population worldwide.

The Roma are comprised of many founder groups of common Indian origins but different socio-cultural characteristics. The Vlax Roma are one of the founder Roma populations characterized by a period of bondage in the historic Romanian principalities, and by the archaic Romanian language. Demographic history suggests different migration routes of Roma populations, especially after their arrival in Mesopotamia and the eastern boundary of the Byzantine Empire. Although various genetic studies of uniparental genetic markers showed a connection between Roma genetic legacy and their migration routes, precise sampling of Roma populations elucidates this relationship in more detail. In this study, we analyzed mitochondrial DNA of 384 Croatian Vlax Roma from two geographic locations in the context of 734 European Roma samples. Our results show that Roma migration routes are marked with two Near-Eastern haplogroups, X2 and U3, whose inverse proportional incidence clearly separates the Balkan and the Vlax Roma from other Roma populations that reached Europe as part of the first migration wave. Spatial and temporal characteristics of these haplogroups indicate a possibility of their admixture with Roma populations before arrival in Europe. Distribution of haplogroup M35 indicates that all Vlax Roma populations descend from one single founder population that might even reach back to the original ancestral Indian population. Founder effects followed by strict endogamy rules can be traced from India to contemporary small, local communities, as in the case of two Croatian Vlax Roma populations that show clear population differentiation despite similar origins and shared demographic history.

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.

We report the psychometric structure of a Croatian translation of the Eysenck Personality Questionnaire-Revised (short-form), its correlations with psychological distress (General Health Questionnaire-30), its heritability, and personality–psychological distress genetic correlations. The setting is a large (≈1000), family-based sample of men and women from an isolated Croatian island. The neuroticism and extraversion traits and the lie scale showed good psychometric characteristics. The translated psychoticism scale was unsatisfactory in this sample. It had a very low internal consistency, probably due in part to heavily biased item responses. There were significant additive genetic contributions to variation in neuroticism, extraversion, and psychological distress. Psychological distress had a very high genetic correlation with neuroticism, and a moderate genetic correlation with extraversion.

The aim of this study is to explore the existing data based on high-resolution phylogenetic studies of Y chromosome variation in populations from Southeastern Europe and elsewhere in Eurasia in order to evaluate the role of the region in the process of the prehistoric colonization of the European continent and the structuring of the modern paternal genetic pool. Even though the distribution and estimated range expansions of major paternal lineages in Southeastern Europe are consistent with the typical European Y chromosome gene pool, the specific role of this region in the process of structuring the European paternal genetic landscape is evident in prehistoric episodes of significant gene flow that diffused from or into the region.

Communities with increased shared ancestry represent invaluable tools for genetic studies of complex traits. "1001 Dalmatians" research program collects biomedical information for genetic epidemiological research from multiple small isolated populations ('metapopulation') in the islands of Dalmatia, Croatia. Random samples of 100 individuals from 10 small island settlements (n

The extent and nature of southeastern Europe (SEE) paternal genetic contribution to the European genetic landscape were explored based on a high-resolution Y chromosome analysis involving 681 males from seven populations in the region. Paternal lineages present in SEE were compared with previously published data from 81 western Eurasian populations and 5,017 Y chromosome samples. The finding that five major haplogroups (E3b1, I1b* (xM26), J2, R1a, and R1b) comprise more than 70% of SEE total genetic variation is consistent with the typical European Y chromosome gene pool. However, distribution of major Y chromosomal lineages and estimated expansion signals clarify the specific role of this region in structuring of European, and particularly Slavic, paternal genetic heritage. Contemporary Slavic paternal gene pool, mostly characterized by the predominance of R1a and I1b* (xM26) and scarcity of E3b1 lineages, is a result of two major prehistoric gene flows with opposite directions: the post-Last Glacial Maximum R1a expansion from east to west, the Younger Dryas-Holocene I1b* (xM26) diffusion out of SEE in addition to subsequent R1a and I1b* (xM26) putative gene flows between eastern Europe and SEE, and a rather weak extent of E3b1 diffusion toward regions nowadays occupied by Slavic-speaking populations.

Eight Y chromosome short tandem repeat (STR) polymorphisms (DYS19, DYS385, DYS389I, DYS389II, DYS390, 13 DYS391, DYS392, and DYS393) were analyzed in the sample of 117 unrelated Albanian males living in Kosovo. A general 14 STR allelic frequency pattern in the Albanian population from Kosovo corresponds to other European populations. Fourty six haplotypes were observed in single copy. The most frequent haplotypes were (DYS19-DYS385-DYS389I-DYS389II-DYS390-16 DYS391-DYS392-DYS393) 14-11/11-13-29-24-11-13-13 (10.26%), 14-14/17-12-28-24-10-11-12 (9.40%), 13-16/18-13-30-17 24-10-11-13 (9.40%), and 14-17/17-13-31-24-10-11-13 (9.40%).

Eight Y chromosome short tandem repeat (STR) polymorphisms (DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393) were analyzed in the sample of 457 unrelated Croatian men. A general STR allelic frequency pattern in Croatians corresponds to other European populations with the exception of the loci DYS19 and DYS389II. The most frequent DYS19 allele was 16, while at the DYS389II the most frequent were alleles 30 and 31. The most frequent Y chromosome haplotype (16-13-13-31-24-11-11-13) was found in 33 individuals (7.22%). One hundred and seventy-four haplotypes (38.07%) were observed in single copies.

Mitochondrial DNA polymorphism was analysed in a sample of 108 Croatians from the Adriatic Island isolate of Hvar. Besides typically European varieties of human maternal lineages, haplogroup F was found in a considerable frequency (8.3%). This haplogroup is most frequent in southeast Asia but has not been reported before in Europe. The genealogical analysis of haplogroup F cases from Hvar suggested founder effect. Subsequent field work was undertaken to sample and analyse 336 persons from three neighbouring islands (Brac, Korcula and Krk) and 379 more persons from all Croatian mainland counties and to determine if haplogroup F is present in the general population. Only one more case was found in one of the mainland cities, with no known ancestors from Hvar Island. The first published phylogenetic analysis of haplogroup F worldwide is presented, applying the median network method, suggesting several scenarios how this maternal lineage may have been added to the Croatian mtDNA pool.

The Roma (Gypsy) are the largest European minority population characterized by poverty, social exclusion as well as by numerous life-style and cultural specificities, which all could have an adverse impact on their cardiovascular health. This study assesses the prevalence of cardiovascular diseases (CVD) risk factors in community-based sample of 430 adult Roma, living in rural area of Croatia, by providing the actual and age-adjusted estimates using the European standard population. The most prominent classical CVD risk phenotypes (blood pressure, obesity, smoking, glucose and lipid profile) were selected, and the standard risk cut-offs were applied. The study has shown that compared to general population of Croatia, the Roma population bears a high CVD risk factors load related to smoking and high glucose level. The CVD risk factors prevalence in Roma also showed important sex and age patterns, the most imposing of which are the findings of higher prevalence of CVD risks in women (especially obesity and triglyceride levels) and the trend of higher body mass index (BMI) level in younger age group (18-34 years) which both stand in contrast to the trends characterizing the general population of Croatia. These findings are complemented by the trend of decreased risk in the oldest age group (65+ years) for all investigated CVD risk factors (with exception of triglycerides level) compared to the 50-64 age group. We conclude that the age and sex CVD risks pattern point to the health transition of this rural Roma population. As we expect the proportion of CVD in the Roma minority of Croatia to increase in the future along with further modernization of their lifestyle, the CVD prevention measures in this population are urgent and should be primarily targeted at women and at the younger segment of this population.

The TP53 gene polymorphisms, Arg72Pro and PIN3 (+16 bp), can have prognostic and predictive value in different cancers including breast cancer. The aim of the present study is to investigate a potential association between different genotypes of these polymorphisms and clinicopathological variables with survival of breast cancer patients in Croatian population. Ninety-four women with sporadic breast cancer were retrospectively analyzed. Median follow-up period was 67.9 months. The effects of basic clinical and histopathological characteristics of tumor on survival were tested by Cox's proportional hazards regression analysis. The TNM stage was associated with overall survival by Kaplan-Meier analysis, univariate, and multivariate Cox's proportional hazards regression analysis, while grade was associated with survival by Kaplan-Meier analysis and univariate Cox's proportional hazards regression analysis. Different genotypes of the Arg72Pro and PIN3 (+16 bp) polymorphisms had no significant impact on survival in breast cancer patients. However, in subgroup of patients treated with chemotherapy without anthracycline, the A2A2 genotype of the PIN3 (+16 bp) polymorphism was associated with poorer overall survival than other genotypes by Kaplan-Meier analysis (P = 0.048). The TP53 polymorphisms, Arg72Pro and PIN3 (+16 bp), had no impact on survival in unselected sporadic breast cancer patients in Croatian population. However, the results support the role of the A2A2 genotype of the PIN3 (+16 bp) polymorphism as a marker for identification of patients that may benefit from anthracycline-containing chemotherapy.

In this paper we will address the case of the Bayash which represent a branch of Romanian speaking Roma living dispersedly in Central, Eastern and Southeastern Europe. In order to start unveiling the genetic history of the Bayash, Y chromosome lineages from Bayash men settled in Northwestern and Eastern Croatia were analyzed and compared with those from European Romani and non-Romani majority populations. Two main layers of Bayash paternal gene pool were identified: ancestral (Indian) and recent (European). The reduced diversity and ancient expansion signals of the ancestral layer suggest a small number of genetically related founders who could have split from one caste or tribe between the 8th and 10th centuries AD, in an unspecified region of the Indian subcontinent. On the other hand, variability of the recent layer mirrors different intensities of gene flow between the Bayash and surrounding Balkan majority populations, most likely during the earlier phase on their migratory route from Southern Balkans via Romania to Croatia. However, the most prominent characteristics of the Bayash and general Romani paternal gene pool is the strong signature of genetic drift, most likely a consequence of a profound founder effect followed by a string of bottleneck events and partitioning into multiple, often mobile groups which were necessary to cope not only with the Indian exodus, but also with various forms of social and economic pressures in historic and modern-day Europe. This peculiar combination of genetic homogeneity and heterogeneity as well as the imprints of endogamy and exogamy in the Bayash and Romani paternal genetic heritage reveal a multifaceted pattern of genetic history which becomes particularly intriguing when it is addressed in the context of local narratives and collective memory regarding the origins and the sense of belonging, relatedness and identity which are often changeable, flexible, subtle, and/or blurred.

Isolation is a known force in evolutionary biology and one of the main factors in speciation. One of the main consequences of severe isolation is reduced mate choice, which results in the occurrence of inbreeding as a result of isolation. We investigated the effects of individual genome-wide heterozygosity measured as the multilocus heterozygosity (MLH) on biochemical markers of hemostasis and inflammation in 1,041 individuals from the island of Vis, Croatia, where inbreeding is prevalent and a wide range of variation in the genome-wide heterozygosity is expected. Assessment of individual genome-wide heterozygosity was based on genome-wide scans using 800 microsatellite (STR) and 317,503 single nucleotide (SNP) polymorphic markers in each examinee. In addition, for each examinee we defined a personal genetic history (PGH) based on genealogical records. The association between PGH and MLH and fibrinogen, D-dimer (Dd), von Willebrand factor (vWF), tissue plasminogen activator (tPA), and C-reactive protein (CRP) was performed with a mixed model, controlling for possible confounding effects. PGH was a significant predictor only for tPA (P < 0.001), whereas neither of the two MLH measures exhibited significant association with any of the investigated traits. The effects of individual genome-wide heterozygosity are most likely expressed in highly polygenically determined traits or in traits that are mediated by rare and recessive genetic variants. Weak associations between PGH and MLH and markers of hemostasis and inflammation suggest that their genetic control may not be highly polygenic and that they could be promising targets for genetic association studies.

The Bayash are a branch of Romanian speaking Roma living dispersedly in Central, Eastern, and Southeastern Europe. To better understand the molecular architecture and origin of the Croatian Bayash paternal gene pool, 151 Bayash Y chromosomes were analyzed for 16 SNPs and 17 STRs and compared with European Romani and non-Romani majority populations from Europe, Turkey, and South Asia. Two main layers of Bayash paternal gene pool were identified: ancestral (Indian) and recent (European). The reduced diversity and expansion signals of H1a patrilineages imply descent from closely related paternal ancestors who could have settled in the Indian subcontinent, possibly as early as between the eighth and tenth centuries AD. The recent layer of the Bayash paternal pool is dominated by a specific subset of E1b1b1a lineages that are not found in the Balkan majority populations. At least two private mutational events occurred in the Bayash during their migrations from the southern Balkans toward Romania. Additional admixture, evident in the low frequencies of typical European haplogroups, J2, R1a, I1, R1b1b2, G, and I2a, took place primarily during the early Bayash settlement in the Balkans and the Romani bondage in Romania. Our results indicate two phenomena in the Bayash and analyzed Roma: a significant preservation of ancestral H1a haplotypes as a result of considerable, but variable level of endogamy and isolation and differential distribution of less frequent, but typical European lineages due to different patterns of the early demographic history in Europe marked by differential admixture and genetic drift.

BACKGROUND: Population isolates are characterized by simplified genetic background and as such present promising opportunities for studying complex diseases. We performed a genome-wide linkage analysis for systolic (SBP) and diastolic blood pressure (DBP) followed up by the association analysis in the Croatian isolated island of Vis, where a very high prevalence of hypertension was reported (75%). METHODS: Variance-components linkage analysis was used to map quantitative trait loci (QTL) for SBP and DBP in 125 families with 1,389 members. Follow-up association analysis was performed in a sample of 421 subjects from the island of Vis. The 15 top-ranking single nucleotide polymorphisms (SNPs) were selected and tested for the association by in silico replication in the British 1958 Birth Cohort DNA Collection. RESULTS: Linkage results showed evidence for a QTL influencing DBP (lod = 1.89) on chromosome 7p14.2 and two QTL influencing SBP (lod = 2.03 on chromosome 1p36 and lod = 1.75 on chromosome 20q13). For the association results, the replication was observed for the rs237484 polymorphism on chromosome 20 that was associated with SBP with the effect size beta = -5.2 (P = 0.001; per A allele) in Vis population and beta = -1.1 (P = 0.04) in the British 1958 Birth Cohort. rs237484 is in proximity to the potassium voltage gate channel gene (KCNB1) and close to the prostaglandin I2 (prostacyclin) synthase gene (PTGIS). CONCLUSIONS: These results provide evidence of a QTL influencing blood pressure (BP) variability in this region and support the notion that the isolated population of the island of Vis is a suitable population for conducting linkage and association analyses of cardiovascular-related phenotypes.

Serogenetic data involving 21 genetic systems were collected from 12 villages on the island of Brač (Yugoslavia) in 1987. Maximum sample size was 709 individuals. The UPGMA dendrogram based on genetic distances was readily interpretable within the contexts of village settlement history, social relationships, and sample size considerations. The gene diversity value (H = 0.3029 ± 0.0119) was both quite high and extremely similar to the average heterozygosity value on the neighboring Pelješac peninsula. Quadratic assignment procedures were used to investigate genetic-linguistic-geographic correspondences. Unlike the Pelješac peninsula, where the distance matrix correlations between genetics and linguistics, genetics and geography, and linguistics and geography were all positive and highly statistically significant; on Brač, only the linguistics-geography correlation achieved statistical significance. Reasons for the differences are sought in the different migrational characteristics of these two population systems, in the complex interaction between evolutionary forces promoting population differentiation (genetic drift) and homogeneity (gene flow), and in known patterns of sociocultural interaction that might have skewed the genetic-geographic associations on Brač.

Researches into health inequalities consistently show disadvantages in health status, morbidity and mortality for various ethnic minority groups. Current knowledge about prevention of cardiovascular diseases (CVD) mainly derives from studies carried out in populations of European origin while the evidences involving Roma population are scarce. Roma, an ethnic minority of northern Indian origin, live in many countries throughout the world and are well known for preserved traditions and resistance to assimilation. They are most often marginalized economically, spatially, politically and in terms of culture. In order to assess the health status and health-related lifestyle attributes, a multidisciplinary anthropological and epidemiological community-based study was carried out including a total of 423 members of the Bayash Roma minority population living in two regions of Croatia (144 men and 279 women, aged 18-84 yrs). Hypertension (HT) was found in 24.8% Bayash Roma (21.5% men and 26.5% women) using standard diagnostic criteria (i.e. BPor = 140/90 mm Hg or taking antihypertensive therapy). The prevalence increases from 5.9% in the age group 18-34 yrs; 35.0% in the age group 35-64 yrs, and 51.4% in the age group 65+ yrs. The prevalence of hypertension in the Bayash Roma is almost half of the magnitude of what is usually reported for the general population of Croatia. It is also lower when compared with other European populations and this finding is not due to comparatively younger average age of the Bayash sample. The significant association of hypertension with age and BMI was confirmed in this study and the importance of non-traditional SES-related CVD risk factors was highlighted. Smoking is a part of traditional Roma life-style and with 70% of smokers almost the entire population is equally exposed to this risk factor in their family environment. Since homogenously distributed, this risk factor did not show to be a significant predictor of hypertension. The extent to which hypertension is influenced by traditional CVD risk factors as well as by some SES indicators was also assessed using a forward stepwise method of the multivariate logistic analysis. Each risk factor was explored as quantitative variable as well as qualitative one using various cut-offs. The best model showed to be the one having age and BMI presented as quantitative variables and sex, region, smoking status, income and schooling years as categorical ones; with cut-off 3 for number of income sources and 8 for the number of schooling years. In spite of the low prevalence of hypertension, the presented results are showing that Bayash Roma are bearing a high CVD risk factors load. We expect that with westernization of their life-style and along with increase of the economic power, the proportion of CVD in population of Bayash Roma will also increase. Therefore, it is important to recognize the need for early cardiovascular disease risk factors prevention in this minority population.

To assess the key characteristics related to living conditions and health in the Bayash Roma population in Baranja and Medimurje regions of Croatia and identify possible demographic and socio-economic sources of variance in self-reported health and reproductive profile.The study comprised a total of 266 adult Bayash individuals from Baranja and 164 from Medimurje (aged 41.3+/-15.1 years). Data on ethno-historical and demographic background, self-identity, life and hygiene conditions, education, employment, health insurance, and health (dietary and smoking habits, reproductive characteristics, diagnosed and undiagnosed health problems, use of medications). were obtained through interviews. Bivariate and multivariate methods were used in statistical analyses.The reported migratory pattern demonstrated that 88.8% of the examinees were born in the region of residence, which showed that the Bayash population was autochthonous and sedentary one. Financially, the Bayash primarily relayed on social welfare support allowance (84%) and child allowance (47%), while merely 2% were permanently and 23% occasionally employed. The proportion of the Bayash who had never attended school amounted to 33.3% (19.3% men and 40.6% women). The access to public water supply system was available to 52.5% of examinees, whereas only 1.7% had public sewage system, and 23.4% had private septic tanks. The most commonly reported health burden were frequent headaches (20.3%), stomach pain (16.3%), anxiety or insomnia (13.1%), hypertension (9.3%), and chronic obstructive pulmonary disease (COPD) (8.6%). The logistic regression identified level of education (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.63-0.94) and access to health insurance (OR, 4.32; 95% CI, 1.46-12.77) as socio-economic/life-style factors playing a significant role in the occurrence of COPD.Our results indicate poor inclusion of the Bayash in the essential social service sectors such as health care, education, and employment, as well as substandard living conditions and unfavorable health-related behavior. Since education and health insurance were found to have significant effects on the observed reproductive status and self-reported health, they should be targeted in planning public health actions for socially marginalized and economically deprived groups.

Seventeen Y-chromosomal short tandem repeats (STRs) (DYS19, DYS385, DYS389I, DYS398II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATA H4.1) were typed in DNA samples from 146 unrelated adult Romani Bayash men from eastern and northwestern Croatia. Analysed Croatian Bayash Romani population represents an example of genetically homogenous population characterised by low levels of haplotype diversity and unique haplotype ratio as well as sharing of the same most frequent (founding) haplotype and its close derivatives by more than one third of the analyzed men. Despite almost exclusive sharing of the same minimal haplotype and its closely related derivates on the background of the Indian Y SNP haplogroup H1, we observed considerable level of genetic differentiation of Romani populations across Europe that should not be neglected in forensic statistics.

This study examines anthropometrically assessed nutritional status of the Bayash, the Roma population from the eastern Croatian region of Baranya, and compares it to the non-Roma general population of eastern Croatia. The analysis of nutritional status and diets is a segment of multidisciplinary anthropological and epidemiological survey of the Roma minority population in Croatia began in 2005. The Bayash are an ethnic group that arrived to Croatia from Romania most likely in the 19th century and speaks a distinct archaic dialect of the Romanian language. The Roma population of Baranya approximates 1,000 according to the 2001 census. The Bayash sample comprised 227 adults aged 18-65yrs. The women fall below the Croatian 10th percentile for stature and men track about the 10th percentile. Both sexes approximate the 25th percentile for body weight. Despite their diminutive size, the Bayash appear to have adequate nutritional status until the age of 35yrs after which their average BMI exceeds the value of 25 kg/m(2) and falls in the overweight category. However, 8% of Bayash are underweight (BMI18.5) in contrast to 1% of the majority population in the region. Underweight rates are especially high in women (11%) compared to men (4%). The prevalence of overweight (BMI 25.0 to 29.9) of 30% is considerably lower than in the majority population (42%) while the prevalence of obesity (BMIor=30.0) of 23% is approximately equal. Overall unsatisfactory nutritional status of the Bayash merits attention. It appears to be the product of unhealthy dietary habits and their socio-economic deprivation that resulted from their poor education and extremely high unemployment.

The dramatic changes in human population structure over the last 200 years have resulted in significant levels of outbreeding, which, in turn, is predicted to lead to increased levels of individual genetic diversity (genome-wide heterozygosity, h). To investigate possible effects of these large demographic changes on global health, we studied the effect of h, measured as relative heterozygosity, h(R), on 15 disease-related traits in four groups of individuals with widely differing ancestral histories (ranging from outbred to inbred) from the Dalmatian islands in Croatia. Higher levels of h(R), estimated using 1184 STR/indel markers, were found in the outbred group (P0.0001) and were associated with lower blood pressure (BP) and total/LDL cholesterol (P = 0.01 and 0.01, respectively) after controlling for other factors, with BP showing a strong sex effect (males P0.5 and females P = 0.002). These findings, if replicated, suggest that h(R) be considered as a genetic risk factor in genetic epidemiological studies on common disease traits. They are consistent with the well-known effects of heterosis (hybrid vigour) described when outcrossing animals and plants. Outbreeding resulting from urbanization and migration from traditional population subgroups may be leading to increasing h(R) and may have beneficial effects on a range of traits associated with human health and disease. Other traits, such as age at menarche, IQ and lifespan, which have been changing during the decades of urbanization, may also have been influenced by demographic factors.

This study examines anthropometrically assessed nutritional status of the Bayash, the Roma population from the eastern Croatian region of Baranya, and compares it to the non-Roma general population of eastern Croatia. The analysis of nutritional status and diets is a segment of multidisciplinary anthropological and epidemiological survey of the Roma minority population in Croatia began in 2005. The Bayash are an ethnic group that arrived to Croatia from Romania most likely in the 19th century and speaks a distinct archaic dialect of the Romanian language. The Roma population of Baranya approximates 1,000 according to the 2001 census. The Bayash sample comprised 227 adults aged 18–65 yrs. The women fall below the Croatian 10th percentile for stature and men track about the 10th percentile. Both sexes approximate the 25th percentile for body weight. Despite their diminutive size, the Bayash appear to have adequate nutritional status until the age of 35 yrs after which their average BMI exceeds the value of 25 kg/m2 and falls in the overweight category. However, 8% of Bayash are underweight (BMIor=30.0) of 23% is approximately equal. Overall unsatisfactory nutritional status of the Bayash merits attention. It appears to be the product of unhealthy dietary habits and their socio-economic deprivation that resulted from their poor education and extremely high unemployment.

The aim of this review is to summarize the existing data collected in high-resolution phylogenetic studies of mitochondrial DNA and Y chromosome variation in mainland and insular Croatian populations. Mitochondrial DNA polymorphisms were explored in 721 individuals by sequencing mtDNA HVS-1 region and screening a selection of 24 restriction fragment length polymorphisms (RFLPs), diagnostic for main Eurasian mtDNA haplogroups. Whereas Y chromosome variation was analyzed in 451 men by using 19 single nucleotide polymorphism (SNP)/indel and 8 short tandem repeat (STR) loci. The phylogeography of mtDNA and Y chromosome variants of Croatians can be adequately explained within typical European maternal and paternal genetic landscape, with the exception of mtDNA haplogroup F and Y-chromosomal haplogroup P* which indicate a connection to Asian populations. Similar to other European and Near Eastern populations, the most frequent mtDNA haplogroups in Croatians were H (41.1%), U5 (10.3%), and J (9.7%). The most frequent Y chromosomal haplogroups in Croatians, I-P37 (41.7%) and R1a-SRY1532 (25%), as well as the observed structuring of Y chromosomal variance reveal a clearly evident Slavic component in the paternal gene pool of contemporary Croatian men. Even though each population and groups of populations are well characterized by maternal and paternal haplogroup distribution, it is important to keep in mind that linking phylogeography of various haplogroups with known historic and prehistoric scenarios should be cautiously performed.

Mitochondrial DNA polymorphisms were analyzed in of 1,610 randomly chosen adult men from 11 different regions from southeastern Europe (Croatians, Bosnians and Herzegovinians, Serbians, Macedonians and Macedonian Romani). MtDNA HVS-I region together with RFLP sites diagnostic for main Euroasian and African mtDNA haplogroups were typed to determine haplogroup frequency distribution. The most frequent haplogroup in studied populations was H with the exception of Macedonian Romani among whom the most frequent were South Asian (Indian) specific variants of haplogroup M. The multidimensional scaling plot showed two clusters of populations and two outliers (Macedonian Romani and the most distant from mainland Croatian island of Korcula). The first cluster was formed by populations from three Croatian islands (Hvar, Krk and Brac) and the second cluster was formed by Macedonians, Serbians, Croatians from mainland and coast, Herzegovinians, Bosnians, Slovenians, Poles and Russians. The present analysis does not address a precise evaluation of phylogenetic relations of studied populations although some conclusions about historical migrations could be noticed. More extended conclusions will be possible after deeper phylogenetic and statistical analyses.

Eight Y chromosome short tandem repeat (STR) polymorphisms (DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393) were analyzed in Macedonians (n = 84) and Macedonian Romani ethnic group (n = 68). Observed allelic frequency distribution and locus diversity values in Macedonians correspond closer to neighboring southeastern European populations than (mostly) western European populations, whereas observed allelic frequency distribution and locus diversity values in Macedonian Romani, as expected based on their Asian (Indian) origin, differ from both neighboring southeastern and (mostly) western European populations. Sixty-six (78.57%) haplotypes appeared in single copies in Macedonians and 15 (22.06%) in Macedonian Romani. The most frequent Macedonian haplotypes (DYS19-DYS385-DYS389I-DYS389II-DYS390-DYS391-DYS392-DYS393) 16-14/15-13-31-24-11-11-13 and 13-16/18-13-30-24-10-11-13 were found in 7 and 6 copies, respectively. The most frequent Macedonian Romani haplotype 15-15/17-14-29-22-10-11-12 was found in 18 males. Total haplotype diversity was 0.9885 +/- 0.0058 (Macedonians) and 0.9008 +/- 0.0242 (Macedonian Romani).

Eight Y-STR polymorphisms (DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393) were analyzed in the sample of 40 Bosnian and 141 Herzegovinian unrelated males. Observed STR allelic frequency pattern and locus diversity values in Bosnians and Herzegovinians correspond closer to neighboring southeastern European populations than previously reported (mostly western) European populations. Thirty one Bosnian haplotypes (91.18%) and 53 Herzegovinian haplotypes (68.83%) appeared in single copies. The most frequent haplotypes (DYS19-DYS385-DYS389I-DYS389II-DYS390-DYS391-DYS392-DYS393) were 16-14/15-13-31-24-11-11-13 (10%) in Bosnians and 16-14/15-13-30-24-11-11-13 (9.93%) and 16-14/15-13-31-24-11-11-13 (7.09%) in Herzegovinians. Total haplotype diversity was 0.9872 +/- 0.0104 (Bosnians) and 0.9777 +/- 0.0053 (Herzegovinians).

This study examines the mitochondrial DNA (mtDNA) diversity of the Croatian-speaking minority of Molise and evaluates its potential genetic relatedness to the neighbouring Italian groups and the Croatian parental population. Intermatch, genetic distance, and admixture analyses highlighted the genetic similarity between the Croatians of Molise and the neighbouring Italian populations and demonstrated that the Croatian-Italian ethnic minority presents features lying between Croatians and Italians. This finding was confirmed by a phylogeographic approach, which revealed both the prevalence of Croatian and the penetrance of Italian maternal lineages in the Croatian community of Molise. These results suggest that there was no reproductive isolation between the two geographically proximate, yet culturally distinct populations living in Italy. The gene flow between the Croatian-Italians and the surrounding Italian populations indicate, therefore, that ethnic consciousness has not created reproductive barriers and that the Croatian-speaking minority of Molise does not represent a reproductively isolated entity.

Eight Y chromosome short tandem repeat (STR) polymorphisms (DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393) were analyzed in the sample of 114 unrelated males living in Serbia. A general STR allelic frequency pattern in Serbians corresponds to other European populations with the exception of loci DYS19, DYS389II and DYS385. Out of ninety identified haplotypes, seventy four (64.91%) appeared in single copies. The most frequent haplotypes (DYS19-DYS385-DYS389I-DYS389II-DYS390-DYS391-DYS392-DYS393) 16-14/15-13-31-24-11-11-13 and 15-15/19-12-28-23-10-12-12 were found in four copies (3.51%). Total haplotype diversity was 0.9947 +/- 0.0021.

Y chromosome variation in 457 Croatian samples was studied using 16 SNPs/indel and eight STR loci. High frequency of haplogroup I in Croatian populations and the phylogeographic pattern in its background STR diversity over Europe make Adriatic coast one likely source of the recolonization of Europe following the Last Glacial Maximum. The higher frequency of I in the southern island populations is contrasted with higher frequency of group R1a chromosomes in the northern island of Krk and in the mainland. R1a frequency, while low in Greeks and Albanians, is highest in Polish, Ukrainian and Russian populations and could be a sign of the Slavic impact in the Balkan region. Haplogroups J, G and E that can be related to the spread of farming characterize the minor part (12.5%) of the Croatian paternal lineages. In one of the southern island (Hvar) populations, we found a relatively high frequency (14%) of lineages belonging to P(*)(xM173) cluster, which is unusual for European populations. Interestingly, the same population also harbored mitochondrial haplogroup F that is virtually absent in European populations - indicating a connection with Central Asian populations, possibly the Avars.

Considerable uncertainty exists regarding the genetic architecture underlying common late-onset human diseases. In particular, the contribution of deleterious recessive alleles has been predicted to be greater for late-onset than for early-onset traits. We have investigated the contribution of recessive alleles to human hypertension by examining the effects of inbreeding on blood pressure (BP) as a quantitative trait in 2760 adult individuals from 25 villages within Croatian island isolates. We found a strong linear relationship between the inbreeding coefficient (F) and both systolic and diastolic BP, indicating that recessive or partially recessive quantitative trait locus (QTL) alleles account for 10-15% of the total variation in BP in this population. An increase in F of 0.01 corresponded to an increase of ∼3 mm Hg in systolic and 2 mm Hg in diastolic BP. Regression of F on BP indicated that at least several hundred (300-600) recessive QTL contribute to BP variability. A model of the distribution of locus effects suggests that the 8-16 QTL of largest effect together account for a maximum of 25% of the dominance variation, while the remaining 75% of the variation is mediated by QTL of very small effect, unlikely to be detectable using current technologies and sample sizes. We infer that recent inbreeding accounts for 36% of all hypertension in this population. The global impact of inbreeding on hypertension may be substantial since, although inbreeding is declining in Western societies, an estimated 1 billion people globally show rates of consanguineous marriages >20%.

The aim of this study was to analyse short tandem repeat (STR) variation using the data on nine loci (D3S1358, vWA, FGA, THO1, TPOX, CSF1PO, D5S818, D13S317, D7S820) in the populations from eight villages on the island of Korcula, Croatia, in order to analyse its genetic and population structure. The analysis of STR data in this study indicated an appreciable degree of genetic homogeneity among the studied village populations on the island, even though a so-called 'east-west dichotomy' and differentiation between the inhabitants of the most recent settlement and the remaining ones was indicated with respect to the loci CSF1PO and TPOX, respectively. The validity of STR markers in assessing genetic structure of small populations and especially in determining the relationships among geographically closely related but reproductively isolated groups remains to be further evaluated, especially in terms of a larger number of studied loci in order to possibly find specific markers useful for resolving genetic patterns of variability at regional levels.

Mitochondrial HVS-I sequences from 10, 365 subjects belonging to 56 populations/geographical regions of western Eurasia and northern Africa were first surveyed for the presence of the T-*C transition at nucleotide position 16298, a mutation which has previously been shown to characterize haplogroup V mtDNAs. All mtDNAs with this mutation were then screened for a number of diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V proper, and the other has been termed "pre~V, " since it predates V phylogenetically. The rather uncommon pre*V tends to be scattered throughout Europe (and northwestern Africa), whereas V attains two peaks of frequency: one situated in southwestern Europe and one in the Saami of northern Scandinavia. Geographical distributions and ages support the scenario that pre*V originated in Europe before the Last Glacial Maximum (LGM), whereas the more recently derived haplogroup V arose in a southwestern European refugium soon after the LGM. The arrival of V in eastern/central Europe, however, occurred much later, possibly with (post-)Neohthic contacts. The distribution of haplogroup V mtDNAs in modern European populations would thus, at least in part, reflect the pattern of postglacial human recolonization from that refugium, affecting even the Saami. Overall, the present study shows that the dissection of mtDNA variation into small and well-defined evolutionary units is an essential step in the identification of spatial frequency patterns. Mass screening of a few markers identified using complete mtDNA sequences promises to be an efficient strategy for inferring features of human prehistory.

Uradu je analizirana antropogenetska struktura šest otočkih/poluotočkih populacija istočnog Jadrana. Ta je struktura izučena na osnovi analize četiriju različitih sustava eritrocitnih antigena te dvaju eritrocitnih izoenzima. Izračunate su vrijednosti frekvencija gena kao i vrijednosti za "genetske udaljenosti" ovih populacija. Na osnovi dobivenih rezultata zaključeno je kako su sve ispitivane populacije tijekom (mikro)evolucije sve do danas zadržale svoje osobitosti, a posebice populacije otoka Korčule i otoka Oliba, koje se odlikuju većom izoliranošću od ostalih izoliranih populacija. Današnja antropogenetska struktura svih ispitivanih populacija ukazuje da su one u svojoj etno-povjesti, u manjoj ili većoj mjeri, pretrpjele brojne promjene, prouzročene ponajprije migra- cijama stanovništva. Međutim, ove su otočke/poluotočke populacije ipak uspjele zadržati određeni broj svojih distinktivnih karakteristika., The anthropogenetic structure of six island/peninsular populations - Brač, Hvar, Korčula, Pelješac, Silba and Olib - of the Eastern Adriatic, Croatia, is analyzed on the basis of the study of four different erythrocyte antigen systems/groups and two erythrocyte isoenzyme systems. Average sample size was 555 individuals. Allele frequencies and genetic distances values were computed. The obtained results point to the fact that all of the populations in question have preserved their separate characteristics in the course of their (micro) evolution to the present day, which is especially noticeable for the island populations of Korčula and Olib, as these populations distinguish themselves from the other studied populations with a greater degree of isolation. The today's genetic structure of the studied populations can be explained through the existing historical and cultural data for the region in question, which in.dicate that they were all, in the course of their ethno-history, influenced by waves of immigration and selective emigrations that must have greatly shaped their present-day population structure., ln der Arbeit wird die anthropogenetische Struktur von sechs Insel- bzw. Halbinselpopulationen der Ostadria enalyslert, Diese Struktur ist aufgrund der Analyse von vier verschiedenen Systemen der erythrozyten Antigene und von zwei erythrozyten Izoenzymen untersucht worden. Es wurden die Werte der Genfrequenz und die Werte der "Genentfernung" dieser Populatinen ausgerechnet. Aufgrund der erzielten Resultate ist man zu dem SchluB gekommen, daB alle befragten Populationen wahrend der (Mikro)Evolution und bis heute und insbesondere die Bev6lkerung der Insel Korčula und Olib, die sich durch gr6Bere Isoliertheit von den anderen isolierten Populationen auszeichnen, ihre Eigenschaften behalten haben. Die heutige anthropogenetische Struktur aller befragten Populationen weist darauf hin, daB sie in ihrer Ethno-Geschichte im kleineren oder gr6Beren MaBe zahlreiche hauptsachuch durch die Migrationen der Bev61kerung verursachte Anderungen hatten. Diesen insularenjhalbinsularen Populationen ist es jedoch gelungen, eine bestimmte Zahl ihrer distinkten Charakteristiken zu behalten.

Serogenetic data on 16 systems and migration data from birthplaces of parent and offspring, collected from 949 inhabitants of 8 vilages on the island of Korcula in the eastern Adriatic (Croatia), were analysed. Geographic distance is not a strong determinant of the population structure on the island. The pattern of the genetic variation now observed derives mainly from history and migration behavior. © 1993 Wiley-Liss, Inc.

Correction to: European Journal of Human Genetics (2003) 11, 535–542. doi: 10.1038/sj.ejhg.5200992

The island of Hvar belongs to the group of Middle Dalmatian Islands, part of the territory of the Republic of Croatia. Geography, ethnohistory and demography of the island of Hvar indicate that analyses of genetic features needs to be based on west-east dichotomy. As part of the anthropology component of the 12th workshop we have studied 105 unrelated inhabitants of Hvar. The DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 gene polymorphism was analysed by PCR-SSOP method using 12th Workshop primers and probes. On the basis of association data together with knowledge of haplotypes previously defined we were able to determine which DR-DQ haplotypes were probably carried by each individual. Thirty-one DRB1, 4 DRB3, 2 DRB5, / DQA1, 16 DQB1 alleles have been identified. Analysis of DRB1-DQA1-DQB1 haplotypes revealed a great diversity. Thirty-four and 38 distinct haplotypes have been identified on the east and west part of the island, respectively. Significant differences were observed between those two parts of island for 1.DRB1*0701 allele (p?0.001) 2.DQA1*0201 allele (p?0.01) and 3.DRB1*0101-DQA*0101-DQB1*0501 haplotype (p?0.05). Unusual haplotype DRB1*0101-DQA*0101-DQB1*0501 was found in 2 individuals from the west and in 3 individuals from the east while unusual haplotype DRB1*1501-DQA1*0102-DQB1*0604 was observed only on the western part. These data support the previously observed west-east dichotomy of the island of Hvar.

Biological structure of the population of the island of Hvar was investigated by using the data on anthropometric variation among nine village populations; 24 body and 14 head dimensions were analysed from 487 male and 437 female adult subjects. Univariate and multivariate analyses revealed heterogeneity among the populations, which says much for the strength of the isolating factors on the island. Using correlations of anthropometric and geographic distance, the observed patterns of variation among villages were closely related to geography, suggesting migration to be an important factor in the formation of the island's population structure. Populations of the examined villages were further grouped to form the population of the eastern part and the population of the western part of the island, which have an ethnodemographic and sociocultural basis. The analyses revealed heterogeneity between the populations and thus provided evidence to support the hypothesis about the existence of the genetically different groups living in the same biotope.

Parameters of Malecot's isolation-by-distance model are estimated for biological (anthropometric head and body dimensions, morphometric dimensions of metacarpal bones, quantitative and qualitative dermatoglyphic traits, and physiological/cardiorespiratory/variables) and linguistic distances and migrational kinship on the island of Korcula and the Peljesac peninsula in Middle Dalmatia, Croatia, Yugoslavia. Resulting parameters and the fit of the model are compared, for both regions, as well as with results of similar analysis in other parts of the world. The fit of the model is highly significant for migrational kinship and linguistic distances and less so for biological traits. Differences between these two populations, which live under basically similar ecological conditions, are explained by variation in biological and sociocultural history.